Contributions
Abstract: P497
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: In the CLAdRIbine Tablets treating multiple sclerosis orallY (CLARITY) study, treatment of patients with relapsing multiple sclerosis (RMS) with cladribine tablets (3.5 and 5.25mg/kg, cumulative) significantly reduced relapse rates, magnetic resonance imaging (MRI) measures and slowed disability progression vs placebo. Recent MS studies have shown that MRI-derived measures of brain volume loss can provide clinically meaningful estimates of brain tissue damage and that this might be slowed down during therapy.
Objectives: To assess the treatment effect on brain volume of therapy with cladribine tablets in patients who participated in the CLARITY study, and to investigate its correlation with disability progression.
Methods: Exploratory analyses were undertaken to measure MRI-derived percentage brain volume change (PBVC) between 6 and 24 months (excluding the first 6 months of treatment to avoid pseudoatrophy), and to assess the correlation of PBVC with 3-month confirmed EDSS progression (3m-CDP). Efficacy objectives were classed as exploratory; all determinations of significance should be regarded as nominal.
Results: The mean annualised PBVC rate (month 6 to 24) was greater in patients treated with placebo (-0.70%, SD 0.787, n=338) than those who received cladribine tablets 3.5 and 5.25mg/kg (-0.56%, SD 0.676, n=336 and -0.57%, SD 0.717, n=351, respectively). Furthermore, PBVC (month 6 to 24) was less in patients treated with cladribine tablets 3.5mg/kg (p=0.019) and 5.25mg/kg (p=0.018) than placebo. After adjusting for treatment group, PBVC (month 6 to 24) in all patients showed a significant correlation with the cumulative probability of 3m-CDP (hazard ratio [HR] 0.753, 95% confidence interval [CI] 0.670-0.846; p< 0.001). Compared with placebo, the risk of disability progression was significantly lower with cladribine tablets 3.5mg/kg (p=0.009) and 5.25mg/kg (p=0.003). Sub-division of patients into PBVC tertiles showed that the highest proportion of patients free from disability progression at 24 months was in the tertile with the lowest PBVC and the smallest proportion of progression-free patients was in the tertile that showed the greatest PBVC.
Conclusions: In the CLARITY study, patients treated with cladribine tablets showed significantly less brain atrophy rates over 2 years than placebo recipients. Interestingly, patients with the least brain atrophy rates showed the highest probability of remaining free from disability progression.
Disclosure: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW).
Nicola de Stefano has received honoraria from Schering, Biogen-Idec, Teva, Novartis, Genzyme, and Merck for consulting services, speaking and travel support. He serves on advisory boards for Merck and Novartis. He has received research grant support from the Italian MS Society.
Antonio Giorgio has no conflicts of interest to declare.
Marco Battaglini has no conflicts of interest to declare.
Alessandro De Leucio has no conflicts of interest to declare.
Gavin Giovannoni serves on advisory boards for Merck, Biogen Idec, and Vertex Pharmaceuticals; has received speaker honoraria and consulting fees from Bayer Schering Pharma, FivePrime, GlaxoSmithKline, GW Pharma, Merck, Biogen Idec, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Aventis, UCB, Vertex Pharmaceuticals, Genzyme Corporation, Ironwood, and Novartis; serves on the Merck speakers bureau; and received research support unrelated to this study from Biogen Idec, Merck, Novartis, and Ironwood.
Christine Hicking is an employee of Merck KGaA, Darmstadt, Germany.
Fernando Dangond is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.
Maria Pia Sormani has received personal compensation for consulting services and for speaking activities from Genzyme, Merck, Teva, Synthon, Actelion, Novartis and Biogen Idec.
Abstract: P497
Type: Poster
Abstract Category: Pathology and pathogenesis of MS - Imaging
Background: In the CLAdRIbine Tablets treating multiple sclerosis orallY (CLARITY) study, treatment of patients with relapsing multiple sclerosis (RMS) with cladribine tablets (3.5 and 5.25mg/kg, cumulative) significantly reduced relapse rates, magnetic resonance imaging (MRI) measures and slowed disability progression vs placebo. Recent MS studies have shown that MRI-derived measures of brain volume loss can provide clinically meaningful estimates of brain tissue damage and that this might be slowed down during therapy.
Objectives: To assess the treatment effect on brain volume of therapy with cladribine tablets in patients who participated in the CLARITY study, and to investigate its correlation with disability progression.
Methods: Exploratory analyses were undertaken to measure MRI-derived percentage brain volume change (PBVC) between 6 and 24 months (excluding the first 6 months of treatment to avoid pseudoatrophy), and to assess the correlation of PBVC with 3-month confirmed EDSS progression (3m-CDP). Efficacy objectives were classed as exploratory; all determinations of significance should be regarded as nominal.
Results: The mean annualised PBVC rate (month 6 to 24) was greater in patients treated with placebo (-0.70%, SD 0.787, n=338) than those who received cladribine tablets 3.5 and 5.25mg/kg (-0.56%, SD 0.676, n=336 and -0.57%, SD 0.717, n=351, respectively). Furthermore, PBVC (month 6 to 24) was less in patients treated with cladribine tablets 3.5mg/kg (p=0.019) and 5.25mg/kg (p=0.018) than placebo. After adjusting for treatment group, PBVC (month 6 to 24) in all patients showed a significant correlation with the cumulative probability of 3m-CDP (hazard ratio [HR] 0.753, 95% confidence interval [CI] 0.670-0.846; p< 0.001). Compared with placebo, the risk of disability progression was significantly lower with cladribine tablets 3.5mg/kg (p=0.009) and 5.25mg/kg (p=0.003). Sub-division of patients into PBVC tertiles showed that the highest proportion of patients free from disability progression at 24 months was in the tertile with the lowest PBVC and the smallest proportion of progression-free patients was in the tertile that showed the greatest PBVC.
Conclusions: In the CLARITY study, patients treated with cladribine tablets showed significantly less brain atrophy rates over 2 years than placebo recipients. Interestingly, patients with the least brain atrophy rates showed the highest probability of remaining free from disability progression.
Disclosure: This study was sponsored by EMD Serono Inc, a business of Merck KGaA, Darmstadt, Germany (in the USA), and Merck Serono SA, Geneva, an affiliate of Merck KGaA Darmstadt, Germany (ROW).
Nicola de Stefano has received honoraria from Schering, Biogen-Idec, Teva, Novartis, Genzyme, and Merck for consulting services, speaking and travel support. He serves on advisory boards for Merck and Novartis. He has received research grant support from the Italian MS Society.
Antonio Giorgio has no conflicts of interest to declare.
Marco Battaglini has no conflicts of interest to declare.
Alessandro De Leucio has no conflicts of interest to declare.
Gavin Giovannoni serves on advisory boards for Merck, Biogen Idec, and Vertex Pharmaceuticals; has received speaker honoraria and consulting fees from Bayer Schering Pharma, FivePrime, GlaxoSmithKline, GW Pharma, Merck, Biogen Idec, Pfizer Inc, Protein Discovery Laboratories, Teva Pharmaceutical Industries Ltd, Sanofi-Aventis, UCB, Vertex Pharmaceuticals, Genzyme Corporation, Ironwood, and Novartis; serves on the Merck speakers bureau; and received research support unrelated to this study from Biogen Idec, Merck, Novartis, and Ironwood.
Christine Hicking is an employee of Merck KGaA, Darmstadt, Germany.
Fernando Dangond is an employee of EMD Serono, Inc., Billerica, USA, a business of Merck KGaA, Massachusetts, USA.
Maria Pia Sormani has received personal compensation for consulting services and for speaking activities from Genzyme, Merck, Teva, Synthon, Actelion, Novartis and Biogen Idec.